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Biomedical subjects

A Killander

Publications and source records attributed to A Killander.

At least 37 records · Page 2Linked to original sources

Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma.

A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, beta 2-micro-globulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (greater than 5.1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed.

Adult↗

Alpha interferon treatment of patients with hairy-cell leukaemia.

We have treated 10 patients with hairy-cell, or hairy-cell-like leukaemia, for more than 6 months, with alpha interferon 3 X 10(6) IV/day I.M. or subcutaneously. All patients were severely pancytopenic before treatment. 7 patients had a typical hairy-cell leukaemia, whereas 3 lacked hairy cells but had the characteristic bone-marrow infiltration. The peripheral blood counts improved in all patients during treatment and the lymphoid infiltration of the bone-marrow was shown to decrease. 1 patient obtained complete remission, 6 partial remission and 3 had a minor response. It is concluded that alpha interferon is effective in the treatment of patients suffering from hairy-cell leukaemia.

Aged↗

Treatment of therapy-resistant Sézary syndrome with Cyclosporin-A: suppression of pruritus, leukaemic T cell activation markers and tumour mass.

A patient with Sézary's syndrome resistant to conventional therapy was successfully treated with Cyclosporin-A (CyA) for 14 months. Pre-treatment in vitro studies showed that the leukaemic T cells were sensitive to therapeutic concentrations of CyA. The patient's pruritus disappeared promptly after 2 d of treatment. The positive effect of CyA on the pruritus was related to the dose and plasma concentrations of the drug. Analysis of leukaemic cell surface markers using monoclonal antibodies showed that episodes of pruritus were correlated with the appearance of cells expressing the T cell "activation" markers interferon- gamma (IFN-gamma) and HLA-DR. This indicated that CyA may control pruritus by suppressing the production/release of lymphokines. Immunohistochemical staining of repeated skin biopsies demonstrated a reduction of infiltrating T cells. Clinically, this was correlated with an improved skin status and a partial regress of palpable lymph node size. Apart from an initial reversible drop in the circulating helper/suppressor T cell ratio, the number of circulating Sézary cells was unaltered during CyA treatment. After 5 months, higher doses of CyA were needed to control symptoms, and this was correlated wit with partial drug resistance also in vitro.

Aged↗

Serum thymidine kinase in vitamin B12 deficiency.

In DNA synthesis deoxythymidine kinase (TK) catalyses the conversion of deoxythymidine to deoxythymidine monophosphate (dTMP) via the 'salvage pathway'. Serum deoxythymidine kinase (S-TK) was measured in this study in 75 patients with vitamin B12 deficiency by a new, very sensitive method, using 125I-deoxyuridine as substrate. Elevated S-TK levels were found in those patients who had developed haemolysis and anaemia and the more advanced the disease the higher the S-TK value. Thus there was a highly significant correlation between S-TK, haemoglobin level and lactic dehydrogenase activity. These findings are consistent with the theory that elevated levels of S-TK are due to release from unstable proliferating tissue.

Anemia, Hypochromic↗

Biochemical markers in non-Hodgkin's lymphoma stages III and IV and prognosis: a multivariate analysis.

The prognostic value of different pretreatment laboratory and clinical findings at diagnosis was assessed in a series of 141 patients with generalized non-Hodgkin's lymphoma. Univariate and multivariate survival analysis (Cox's regression model) was performed, using serum analysis of deoxythymidine kinase (S-TK), beta 2-microglobulin, lactic dehydrogenase, alpha 1-acid glycoprotein = orosomucoid (S-alpha 1 AGP), haptoglobin and ferritin. In addition, Hb and the erythrocyte sedimentation rate (ESR) were measured. The clinical variables were age, presence or absence of B-symptoms, histopathology ('low-grade'; 'intermediate grade' and 'high-grade' malignancy) and bone marrow involvement. Of the 8 biochemical markers, all except Hb and the ESR showed a significant relationship to survival. Among the clinical variables, this finding was made for B-symptoms and histopathology. Using a multivariate analysis on all variables, S-TK was found to be the best factor for predicting duration of survival. The only significant additional information was provided by S-alpha 1 AGP. When only the clinical variables were taken into account, it was found that histopathology added significant information to that yielded by B-symptoms in the prediction of the survival time. When the biochemical variables were added to this model, only S-TK was of significant additional prognostic value.

Adolescent↗

Serum beta 2-microglobulin in malignant lymphoma.

Serum beta 2-microglobulin (S-beta 2m) was measured at diagnosis in 189 patients with malignant lymphoma, all with a normal serum creatinine clearance. The diagnosis was non-Hodgkin's lymphoma (NHL) in 149 patients and Hodgkin's disease (HD) in 40. Among the NHL group, S-beta 2m was raised (greater than 3.0 mg/l) in 15% of patients with Stage I and II and in 65% of those with Stage III and IV. The corresponding frequencies for HD were 11% and 83% respectively. In NHL, a high pretreatment level of S-beta 2m was found to be a poor prognostic sign in all stages. Patients in Stage I and II with an elevated pretreatment level of S-beta 2m had a higher relapse rate than those with normal S-beta 2m. In Stage III and IV patients with initial levels greater than 3.5 mg/l, the survival was significantly shorter than in those with initial values of less than 3.5 mg/l. A lower mean S-beta 2m value was found in Stage III and IV patients who achieved complete remission than in those who did not. Serial determinations of S-beta 2m in 23 patients with NHL showed that increased pretreatment levels became normal when remission was achieved and increased again in relapse. Thus the S-beta 2m provides valuable prognostic information in this group of patients.

Adolescent↗

Intermittent high-dose melphalan/prednisone vs continuous low-dose melphalan treatment in multiple myeloma.

Patients with newly diagnosed multiple myeloma were randomly allotted to an intermittent high-dose melphalan/prednisone (MP) treatment (120 patients) or a continuous low-dose melphalan (M) regimen (99 patients). The median observation time was 59 months (range 33-84). Response to therapy was obtained in 45% of the MP group and 31% of the M group (P less than 0.05). No significant difference in response with regard to clinical stage was noted. Median survival was 36 months in the MP group and 29 months in the M group. Survival was longer in stage I and II myeloma than in the stage III cases, at least in the MP group. The median and 5-yr survival rates in stages I and II were significantly better in the MP than in the M group. Response to therapy was associated with length of survival, median survival being 62 months in responding patients and 20 months in non-responders. The MP and M groups did not differ in this respect.

Adult↗

Evaluation of euglobulin clot lysis time as a screening method for determination of blood plasma fibrinolytic activity after venous occlusion.

Determination of the fibrinolytic activity should be performed in patients with recurrent thromboembolic disease. As a screening procedure we suggest the euglobulin clot lysis time test after venous occlusion. This test is sufficiently reliable and easier to perform than the fibrin plate method, especially outside coagulation laboratories.

Adult↗

Prednimustine and vincristine compared with cytosine arabinoside and thioguanine for treatment of elderly patients with acute nonlymphoblastic leukemia.

Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine + vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 patients randomized to prednimustine and vincristine (15 adequately treated), three entered a complete remission and one a partial remission. Four further patients went into complete remission after a switch to other treatment modalities. Of 34 patients randomized to cycles of ARA-C and thioguanine (22 adequately treated), four entered a complete remission and three a partial remission with the correct program. One patient entered a remission with intermittent cytosine arabinoside + thioguanine (wrong program) and one further patient entered a complete remission after a switch to prednimustine and vincristine. Prednimustine + vincristine did not appear to be superior to treatment with cytosine arabinoside thioguanine cycles for elderly patients with ANLL.

Acute Disease↗

Cyclosporin-A is selectively cytotoxic to human leukemic T cells in vitro.

We have studied the antileukemic effects of cyclosporin-A (CyA) on the cells of a number of human hematopoietic biopsies and established cell lines in vitro. Cya killed the tumor cells but not the nonmalignant control cells from three of four patients with T-lymphocytic leukemia/lymphoma at concentrations comparable to those recommended in clinical long-term immunosuppressive therapy. The leukemic cells from 7 patients with B-type chronic lymphocytic leukemia were insensitive to CyA. The drug was cytostatic and cytolytic to three of five T-lymphoblastic leukemia cell lines tested. With the possible exception of a plasma cell line, all other control cell lines (B-lymphocytic lymphoma, histiocytic lymphoma, fibroblast, and glia cell lines) were resistant to CyA. These observations indicate that CyA or its derivatives may be useful as a highly selective antitumor agent in different T-cell malignancies.

B-Lymphocytes↗

Comparison of daunorubicin and daunorubicin-DNA complex in the treatment of acute nonlymphoblastic leukemia.

Sixty consecutive patients, 15-60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1 + ARA-C 2 mg/kg body weight on days 1-5; R2, DNR 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8. Maintenance treatment consisted of monthly courses of DNR 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1-5, alternating with thioguanine 2 mg/kg PO on days 1-5 combined with ARA-C 1 mg/kg IV on days 1-5. Fourteen patients of 20 went into complete remission with R1, 13 or 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer 'minor' cardiac abnormalities than treatment with free DNR in the same dosage schedule.

Acute Disease↗

Serum ferritin in the regulation of iron therapy in blood donors.

12 regular blood donors were selected on the basis of subnormal serum ferritin levels as a criterion for iron deficiency. It was found that all had high transferrin levels but only 5 had subnormal serum iron or transferrin saturation. The donors were given oral iron therapy in a dose of 2,800 mg between each phlebotomy, and the donation interval was standardized to 8 weeks. Test samples were collected every 4th week. After an initial rise in ferritin during the first 2 months, 6 of the donors again had subnormal serum ferritin levels, and the iron dose was therefore doubled after 32 weeks. Following this, all subjects taking the higher dose had normal ferritin values and stainable marrow iron was found at the end of the study, after 92 weeks. 3 subjects did not take the higher dose, had no raised serum ferritin level or stainable hemosiderin. It is concluded that serum ferritin estimation can be used to monitor the therapy in blood donors so that a satisfactory amount of iron is stored.

Blood Donors↗

Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: a preliminary report.

Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.

Acute Disease↗

Serum ferritin during infection. A longitudinal study in renal transplant patients.

In order to follow the dynamics in the reaction of iron kinetic variables to acute infection, 8 renal transplantation patients were followed with test samples every second or third day for about two months. It was found that they just as previously shown in otherwise healthy subjects, responded to acute infection with a rise in serum ferritin levels, sometimes to very high values. In most cases the ferritin elevation started within two days after the onset of fever. The peak was reached within a week, except when very high values were obtained. The fall in serum ferritin after recovery from infection was much faster than in previously investigated groups of patients: the plasma half disappearance time for ferritin in one case was but 1.5 days. Transferrin did not change in response to infection. The expected fall in serum iron during infection was often absent and sometimes obscured by unexpected, sharp peaks in serum iron, which bore a temporal relationship to episodes of transplant rejection in 7 of 12 cases.

Acute Disease↗

Oxymetholone treatment in myelofibrosis.

In order to study the effect of oxymetholone therapy in advanced myelofibrosis, 11 patients (4 females, 7 males) were given, 3--5 mg per kg body weight, long-term oxymetholone treatment in a prospective multicenter study. Five cases had previously had a diagnosis of polycythemia vera. All patients had anemia initially, 4 leukocytopenia and 10 thrombocytopenia in addition. Hepato-splenomegaly was present in all cases but in varying degree. Five patients required regular blood transfusions before treatment. In 9 of the 15 courses given, there was normalization of the peripheral blood or substantial improvement (better than 3 g hemoglobin/dl or 50 X 10(9) platelets/1) after androgens. Significant effects were noted both on hemoglobin values and platelet counts. The need for blood transfusions ceased completely in all 5 cases. When oxymetholone treatment was reduced or interrupted 4 patients relapsed; 2 of them responded to a renewed course. The red cell counts returned to previous polycythemic values in one patient and another died from acute leukemia. The results of this study suggest that androgens might be of value in advanced cases of myelofibrosis with transfusion-requiring anemia or severe thrombocytopenia.

Aged↗